University of Groningen
Cost-effectiveness analysis on elderly pneumococcal vaccination in the Netherlands
Zeevat, F; van der Schans, J; Boersma, W G; Boersma, C; Postma, M J
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Vaccine
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10.1016/j.vaccine.2019.08.051
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Zeevat, F., van der Schans, J., Boersma, W. G., Boersma, C., & Postma, M. J. (2019). Cost-effectiveness
analysis on elderly pneumococcal vaccination in the Netherlands: Challenging the Dutch Health Council's
advice. Vaccine, 37(43), 6282-6284. https://doi.org/10.1016/j.vaccine.2019.08.051
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Short communication
Cost-effectiveness analysis on elderly pneumococcal vaccination in the
Netherlands: Challenging the Dutch Health Council’s advice
F. Zeevat
a,⇑, J. van der Schans
a, W.G. Boersma
b, C. Boersma
a, M.J. Postma
a,c,daDepartment of Health Sciences, University of Groningen, University Medical Centre, Groningen, Netherlands b
Department of Lung Diseases, Nortwest Clinics, Alkmaar, Netherlands
c
Unit of PharmacoTherapy, -Epidemiology & Economics, University of Groningen, Department of Pharmacy, Groningen, Netherlands
d
Department of Economics, Econometrics & Finance, University of Groningen, Faculty of Economics & Business, Groningen, Netherlands
a r t i c l e i n f o
Article history:
Received 25 February 2019 Received in revised form 2 July 2019 Accepted 21 August 2019
Available online 9 September 2019 Keywords:
Elderly pneumococcal vaccination Polysaccharide vaccine
Conjugated vaccine Cost-effectiveness The Netherlands
Dutch Health Council advice
a b s t r a c t
Recently, the Dutch Health Council advised on elderly pneumococcal vaccination favouring the conven-tional polysaccharide vaccine over the novel conjugated vaccine. This advice was strongly inspired by a cost-effectiveness analysis considered to show favourable outcomes for the polysaccharide but not for the conjugated vaccine. We argue that using the same data and methods as presented by the Health Council, a different perspective on the results leads to a conclusion that not only the polysaccharide but also the conjugated pneumococcal vaccine is cost-effective. Our alternative perspective concerns the use of realistic vaccine prices, and applying an adequate time horizon for cost-effectiveness mod-elling. Notably, for one-off vaccination of 65-years old elderly, in all investigated analyses, also the con-jugated vaccine seems cost-effective; i.e. well below the threshold of€20,000 per quality-adjusted life year, reflecting the most stringent threshold used for vaccines in the Netherlands.
Ó 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
1. Introduction
A recent advice of the Dutch Health Council recommends uptake of a pneumococcal vaccination program for elderly using the conventional 23-valent pneumococcal polysaccharide vaccine
(PPV23) [1]. The Dutch authorities have analysed pneumococcal
vaccination several times, but so far the Netherlands had been among the 8 out of 28 EU-countries that until recently never rec-ommended or implemented an elderly vaccination program using
PPV23 [2]. The quest for the Health Council’s advice was also
inspired by recent local evidence that has become available on the alternative novel 13-valent pneumococcal conjugated vaccine (PCV13) from a large randomized clinical trial among approxi-mately 80,000 Dutch individuals aged 65-years and over (‘‘community-acquired pneumonia immunization trial in adults”; CAPITA), potentially warranting a PCV13-based elderly
pneumo-coccal vaccination program[3].
As in many countries nowadays, health technology assessment (HTA) provides a core aspect in the Dutch national authorities’ approach to advise and decide on the introduction of a new vacci-nation campaign. Within the context of healthcare decision-making, cost-effectiveness analysis – as one of the seven criteria
for introducing new vaccinations[4]– constitutes a crucial
ele-ment, with the cost per quality-adjusted life year (QALY) generally
as its main outcome. Informed by a separate analysis [5], the
Health Council inferred that universal elderly vaccination with PPV23 is effective, whereas PCV13 was estimated not
cost-effective, applying a strict threshold cost-effectiveness at
€
20,000per QALY, a limited time horizon and officially listed prices for
individual use[1]. This result can be considered surprising as it
contradicts previous Dutch cost-effectiveness analyses on PCV13
in elderly persons[6,7], also based on CAPITA.
Here, we argue that a different view on the same economic data would result in a different conclusion in which both vaccines could be considered cost-effective options if a lifetime time horizon for analysis is taken and/or realistic pricing is considered; well below
the aforementioned lowest limit for cost-effectiveness at
€
20,000per QALY for the Netherlands[8]. To derive our arguments,
sec-ondary analysis on selected data from the published
cost-effectiveness study[5]was performed.
2. A broader health-economic perspective on the dutch health council advice
With the core role for the cost-effectiveness analysis in the Dutch recommendation for PPV23 to be implemented in a future
universal elderly pneumococcal vaccination program[1], it seems
https://doi.org/10.1016/j.vaccine.2019.08.051
0264-410X/Ó 2019 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
⇑Corresponding author.
E-mail address:f.zeevat@rug.nl(F. Zeevat).
Vaccine 37 (2019) 6282–6284
Contents lists available atScienceDirect
Vaccine
appropriate to review this analysis in more detail[5]. In the eco-nomic model, evidence on the effectiveness of PCV13 against inva-sive pneumococcal disease and pneumonia was taken from the
CAPITA-study (Table 1). For PPV23, effectiveness against IPD was
obtained from a recent meta-analysis[9], whereas for effectiveness
against pneumonia it was not possible to identify appropriate data. An assumption based on the contribution of the PPV23 serotypes in the overall serotype distribution in the Netherlands was made for PPV23’s effectiveness on pneumonia. For PCV13 lasting protection up to 15 years was assumed as well as long-term herd immunity effects, whereas for PPV23 only short-term protection was
assumed[5]. Finally, we note that list prices were used to reflect
costs of vaccination.
Over the 10-year time horizon mostly applied in the Health Council analyses, QALY gains for PCV13 surpass those by PPV23 with 196 as an aggregate for the whole of the Netherlands, for vac-cinating 10 cohorts of 65-years old and measuring benefits during those 10 years only. The corresponding cost-effectiveness
esti-mated was
€
44,000 per QALY for PCV13 and labelled ‘‘notcost-effective”[5]. This relatively short time horizon of 10-years was
used, instead of the generally preferred lifetime time horizon. Guidelines for pharmacoeconomic research recommends the
life-time life-time horizon (for example, the Dutch guidelines[10]) to allow
for adequate capturing of the whole spectrum of costs and benefits
[11]. Specifically, the 10-year time horizon may be considered too
short to capture all impacts of, in particular, for PCV13 with longer lasting protective effects thus underestimating the economic value of PCV13. Notably, in the last cohorts vaccinated in the 10-year time period, adequate time to reap the benefits of vaccination at all is not allowed in the model. In sensitivity analyses, the model was evaluated over longer time frames, including lifetime. Based on applying lifetime costs and effects, cost-effectiveness for
PCV13 was indeed estimated much lower at
€
15,400 per QALYfor vaccinating 65-years olds[5], below the limit of
€
20,000 perQALY.
It is well known that list prices – as applied for general pharma-cies – do not reflect the costs of vaccines for the public health authorities within public programs. For example, costs reported for the Dutch public authorities for PCV10 and the HPV-vaccine included in the Dutch national vaccination program are ranging
from
€
17 to€
23 [12], reflecting grossly 15–40% of listed prices[13]. Obviously, the exact level of discounts provided is
confiden-tial and is likely to be dependent on the type of program, the
speci-fic disease targeted with vaccination, the availability of
competitors, the design of the tenders and the negotiation power of the parties involved. However, that the net price will be substan-tially below the list price seems a reasonable assumption. An assumed price reduction of 50% would result in a
cost-effectiveness ratio of
€
18,900 per QALY for PCV13 (calculationsby the authors on the reported data[1,5]with a limited 10-year
time horizon).
Combining a 50% price reduction and the longer time horizon in a secondary analysis on those data reported in the published paper
[5]resulted in cost-effectiveness ratios listed inTable 2, with var-ious scenarios estimated in the lifetime time horizon. We build on the scarcely reported lifetime cost-effectiveness results in the pub-lished data[5]; i.e., two cost-effectiveness ratios (CERs) for the age
group of 65-years olds at
€
15,400 and€
3,200 per QALY for PCV13and PPV23, respectively (base-case estimates). Building on this reported base-case, estimated savings and QALYs were calculated per case averted over 10-years period and subsequently used for estimating total savings and QALYs gained over the lifetime period (see Annex for details on methodology). Sensitivity analysis was performed on the savings and QALYs per case, by varying + and 25% in the estimates, to derive uncertainty intervals. As, cur-rently, no elderly pneumococcal vaccination is performed in the Netherlands, the comparison of PCV13 and PVV23 with absence of vaccination - as made in the original comparison of the Health Council – seems an appropriate one. Yet, health-economics theory might also warrant an incremental cost-effectiveness analysis relating the likely more expensive alternative (PCV13) to the less
expensive one (PPV23).Table 2, additionally mentions these
incre-mental cost-effectiveness ratios (ICERs). Notably, the base-case
ICER for PCV13 over PPV23 was estimated at
€
31,400 (uncertaintyinterval:
€
26,100;€
46,300) per QALY at baseline, and acorre-sponding break-even price of PCV13 at
€
20,000 per QALY of61.2% (50.7–69.7%) of the list price. Finally, as evidence on effec-tiveness for community-acquired pneumonia (CAP) is scarce and
contradictory [1], we also analysed absence of effectiveness of
PPV23 on CAP, using the same secondary-data analysis methodol-ogy as outlined above (and in the Annex).
3. Discussion
It is likely that the integrative nature of the economic model is very attractive to authorities. However, we need to stay critical about such analysis. Above, we have shown that the same data used for the Dutch Health Council’s advice on elderly pneumococ-cal vaccination can – or likely should - result in a different conclu-sion on the economic attractiveness of elderly vaccination with PCV13. In our alternative approach, almost all analyses investi-gated indicated a favourable cost-effectiveness of PCV13 if
evalu-ated at
€
20,000 per QALY. This result contrasts the HealthCouncil report[1]that labelled PCV13 as not-cost-effective.
We argue that the time horizon of 10 years – that was mostly
considered in the Health Council report[1,4]- is too low to capture
the full benefits of PCV13 vaccination and seems in contrast with international guidelines that favour a long, ideally, lifetime time horizon. Changing to a long-term time horizon acknowledges the full benefits of PCV13 and consequently, cost-effectiveness is low-ered to acceptable levels. Particularly, both the adequate longer time horizon as well as expected reductions on the list price
indi-cate a cost-effectiveness for PCV13 well below the strict
€
20,000-per-QALY threshold. The Health Council’s focus on the short 10-year time horizon results, in contrast to international guidelines, was motivated by pointing to the uncertainty in future trends
[1,5]. The issue of uncertainty raised by the authors is fair, in par-ticular for pneumococcal epidemiology, however, should possibly better be dealt with by applying adequate discount rates on future health benefits and savings according to standard health-economic theory rather than deviating from the preferred lifetime time hori-zon. Discounting was indeed performed in the analysis according to the Dutch health-economic guidelines. Discounting as well as reducing the time-horizon seems like ‘‘double counting” in penal-ising for uncertainty, which needs to be avoided. Notably, a recent report by the National Institute for Health & Care Excellence (NICE)
Table 1
Core assumptions in the Dutch cost-effectiveness model for PCV13 versus PPV23[5].
PPV23 PCV13
Vaccine costs (list prices) €21.20 €72.67 Vaccine effectiveness 1st 5 years
IPD 56-0%[9]* 75%[3]
CAP 20-0% [assumed] 38%[3]
Vaccine effectiveness next 10 years
IPD 0% 75–0% [assumed]**
Pneumonia 0% 38–0% [assumed]**
*Linear decrease from year 1 to 5; **Linear decrease from maximum in 1st 5 years to 0% in 10 years; IPD = invasive pneumococcal disease; CAP = vaccine-type hospi-talised community-acquired pneumonia.
as well as the Joint Committee of Vaccination & Immunization (JCVI) reinforced the use of a lifetime time horizon and adequate
discounting, in particular for vaccines [14]. Whereas a lifetime
approach may be considered optimal, already after a finite period the vast majority of savings and health gains would be harvested. In particular, with average life expectancy at 65 years at approxi-mately 20 years, a time horizon of 20 years after the last cohort considered is vaccinated could be sufficient to capture the vast majority of benefits. This is however still far more than 10 years.
Some further analyses seem warranted. Notably, the Health Council’s report did not follow the societal perspective as preferred
in the Dutch guidelines[10]. This perspective would, for example,
advocate inclusion of sickness leave and production losses due to pneumonia. These can be significant for those in their sixties and become increasingly important, considering the increasing pension age in the Netherlands. In this respect the cost-effectiveness esti-mates, in particular, those for PCV13 given the higher initial pro-tection, should again be conceived as underestimates. Finally, we note that some potentially relevant calculations were not reported in the Dutch Health Council report and could also not be deduced
from the reported data[1,5]. A combined strategy of initial
vacci-nation with PCV13 and re-vaccivacci-nation with PPV23 was not anal-ysed but has been suggested in the literature as a potentially
cost-effective approach [15,16]. For Germany, this sequential
approach applied to all individuals at risk was estimated
cost-effective at
€
14,000 per QALY from the societal perspective,vary-ing from
€
3,300 to€
29,600 per QALY in scenario analysis[16].In conclusion, instead of the cost-effectiveness results pre-sented by the Dutch Health Council that favour PPV23 over PCV13 – the latter labelled as ‘‘not cost-effective” – a more appro-priate selection of analyses that adheres to international pharma-coeconomic guidelines on time horizon and acknowledges economies of scale shows that rather both vaccination strategies have potentials of being (highly) cost-effective. Best estimates of cost-effectiveness for PCV13 are consistently (well) below
€
20,000 per QALY, which reflects an often used threshold forvac-cines. We conclude that an adequate and consistent weighting of the analyses of the Dutch Health Council makes PCV13 elderly vac-cination more economically attractive than suggested, giving rise to two potentially cost-effective options of elderly pneumococcal vaccination in the Netherlands: both PPV23 as well as PCV13. Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by an unrestricted grant from Pfizer, the Netherlands. Pfizer was not involved in the design, con-duction and reporting of the analyses and paper. Prof Maarten J. Postma reports grants and honoraria from various pharmaceutical companies, including all major industries developing, producing and marketing pneumococcal and other vaccines.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.vaccine.2019.08.051. References
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Table 2
Selected exploratory scenarios from secondary data analysis on reported cost-effectiveness information[5]estimating cost-effectiveness ratios (CERs) and incremental CERs (ICERs) in€/QALY, with corresponding uncertainty intervals. Scenarios are based on reported base-case CERs of€15,414 and€3195 for PCV13 and PPV23, respectively.
Scenarios CER PCV13 CER PPV23 ICER
1. Reduced price PCV13 €4,390 [3,217–5,202] €3,195 NA* €5,950 [3,244–8,213]
2. Reduced price both €4,390 [3,217–5,202] CS** [CS-CS] €13,364 [11,237–15,836]
3. No CAP PPV23 €15,414 NA* €12,917 [10,265–14,920] €16,771 [15,626–19,429]
4. No CAP PPV23 and reduced price PCV13 €4,390 [3,217–5,202] €12,917 [10,265–14,920] CS** [CS-1,937] 5. No CAP PPV23 and reduced price both €4,390 [3,217–5,202] €3,782 [2,516–4,995] €4,720 [2,222–6,535]
*
NA: not applicable as this was the input in our back calculation process for net costs and net QALY gains in the estimation procedure outlined above;
**
CS: cost saving; CAP = vaccine-type hospitalised community-acquired pneumonia; CER = cost-effectiveness ratio; ICER = incremental cost-effectiveness ratio; PCV13 = 13-valent pneumococcal conjugated vaccine; PPV23 = 23-13-valent pneumococcal polysaccharide vaccine.
